The present invention relates to the fields of therapy and prophylaxis and, more particularly, to methods for evaluating various parameters related to the therapeutic and/or prophylactic treatment of solid neoplasms (tumors), such as osteosarcoma, in humans.
Osteosarcoma is a malignancy which occurs primarily during the second decade of life in humans. Although at present there is no known mode of successful long-term therapy for osteosarcoma, various investigators have proposed forms of adjuvant chemotherapy for delaying the occurrence of histologically evident metastases and clinical relapse. See: Cortes, E. P., et al. "Amputation And Adriamycin In Primary Osteosarcoma. A Five Year Report", Cancer Treat. Rep., 62, 271-277 (1978); Jaffe, N., et al., "High-Dose Methotrexate In Osteogenic Sarcoma. A Five Year Experience", Cancer Treat. Rep., 62, 259-264 (1978); Sutow, W. W., et al., "Multi-Drug Chemotherapy In Pulmonary Treatment Of Osteosarcoma", J. Bone Joint Surg., 58A, 629-633 (1976).
Among the more promising potential avenues for treatment of osteosarcoma in humans is the use of osteosarcoma-specific dialyzable leukocyte extract (DLE). In studies conducted by us and others in our group, the immunoprophylactic potency of osteosarcoma-specific DLE against lung metastases in humans was shown to be quite promising, as five of six patients without previous overt tumor who received the osteosarcoma-specific DLE for twenty-four months survived for at least five years. Levin, A. S., Byers, V. S., Fudenberg, H. H., Wybran, J., Hackett, A. J., Johnston, J. O., and Spitler, L. E., "Osteogenic Sarcoma: Immunologic Parameters Before And During Immunotherapy With Tumor-Specific Transfer Factor", J. Clin. Invest., 55, 487-499 (1975); Byers, V. S., LeCam, L., Levin, A. S., Johnston, J. O., and Hackett, A. J., "Immunotherapy Of Osteogenic Sarcoma With Transfer Factor. Long Term Follow Up", Cancer Immunol. Immunother., 6, 243-253 (1979).
Among the most difficult problems in seeking effective therapeutic and prophylactic treatment of any disease or condition in humans is the need for a means of evaluating a particular drug or treatment regimen without having to resort to experimentation with human subjects themselves. Obviously, concerns are ever-present with respect to the use of human subjects as hosts in which to evaluate potential treatments having unknown or poorly understood direct effects and/or side effects. Moreover, as is often the case, even treatments which are known to be safe and effective for humans in general desirably should be patterned to the particular subject in question, either in terms of required dosages, administration regimens, required adjuvants, and other like considerations.
As a consequence of this time-honored and obvious limitation on evaluating parameters related to treatment of human subjects, investigators have long resorted to, and continue to search for, means for providing objective indices of effectiveness and consequences of particular treatments in humans. Numerous techniques are known for use of in vitro assays (utilizing either the cells or fluids of a human subject or of an animal subject) or in vivo studies using animal subjects as predictors of effects in human subjects of various treatments, establishing proper dosages for use in humans and the like. However, in many cases the degree to which either in vivo animal studies or in vitro assays accurately mimic conditions encountered in human subjects is limited and, hence, such techniques cannot be relied upon as indicators of human subject response to particular treatments.
In the field of osteosarcoma therapy and prophylaxis, animal models have been proposed for study of the potential effect of a variety of immunomodulators and/or chemotherapeutic agents on human subjects. See, for example, Singh, I., Tsang, K. Y. and Blakemore, W. S., "A Model for Human Osteosarcoma In Hamsters", Clin. Orthop. Rel. Res., 144, 305-310 (1979); Tsang, K. Y. and Fudenberg, H. H., "Isoprinosine As An Immunopotentiator In An Animal Model Of Human Osteosarcoma", Int. J. Immunopharmac., 3, 383-389 (1981). Although to certain degrees successful as predictors of human response to particular treatments, further improvement in these models is required in order to attain higher degrees of accuracy in predicting human responses and developing other information needed in evaluating potential therapeutic and prophylactic treatments. In particular, improvement is required in providing animal models not only for osteosarcoma tumors, but also with respect to all solid neoplasms in humans.
In accordance with the present invention, an animal model is described which behaves biologically in a manner closely similar, if not identical, to that of humans with solid neoplasms such as osteosarcoma, fibrosarcoma, pancreatic adenosarcoma, and the like, and hence provides a means for evaluating parameters related to use of therapeutic and/or prophylactic agents and treatments in humans.